The Mannich reaction, first discovered in the early 20th century, is among the most robust reactions known to produce nitrogen-containing compounds. In a classic intermolecular Mannich reaction, an aldehyde, an amine and an α-acidic carbonyl compound react to form a β-amino carbonyl compound. Recent progress in this area, including modified imine donors and well-explored catalyst systems, has made available a wide variety of asymmetric α-functionalizations of carbonyl compounds. However, to date, asymmetric Mannich-type reactions to establish α-quaternary carbonyl compounds have been limited to specialized substrate classes.
There exists a need for methods that enable access to α-quaternary Mannich Adducts, particularly enantioselective methods to provide enantioenriched products.